Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review

Abstract

BackgroundThe optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear.Materials and methodsWe systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes.ResultsThe search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefit for trifluridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in efficacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy.ConclusionsThese findings support the introduction of an approved agent such as trifluridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second-line treatment.

Metastatic Colorectal Carcinoma after Second Progression and the Role of Trifluridine-Tipiracil (TAS-102) in Switzerland

“…Rechallenge therapy, i.e., administration of a previously given regimen of chemotherapy with or without the same antibodies (e.g., bevacizumab or anti-EGFR related to a molecular tumor profile), may be an option for selected patients [22]. Oncol Res Treat 2020;43:237-244 DOI: 10.1159/000506080 A possible explanation for the efficacy of such a rechallenge strategy is that mCRC comprises heterogeneous tumor clones.…”

“…Rechallenge with an oxaliplatin-based chemotherapy can therefore represent an option for the treatment of refractory mCRC and it is therefore listed in the joint ESMO [3], German S3 [4] and NCCN [5] guidelines. Rechallenge with a chemotherapy combination such as FOL-FOX or FOLFIRI, however, has not been studied prospectively [22].…”

“…Overall, the evidence for the success of a rechallenge strategy with cetuximab or bevacizumab with or without chemotherapy such as oxaliplatin and irinotecan is limited. The results of such studies must be interpreted with caution due to the small sample sizes and a lack of appropriate controls [22]. Further prospective clinical trials are warranted before this option can routinely be considered in clinical practice.…”

Gilteritinib induces PUMA‐dependent apoptotic cell death via AKT/GSK‐3β/NF‐κB pathway in colorectal cancer cells

“…[1][2][3] For the treatment for CRC, chemotherapy cytotoxic drugs, such as oxaliplatin, 5-fluorouracil (5-FU) and irinotecan, are used in specific combinations, but are not very efficient and cause major side effects because of limited specificity. 4,5 For instance, Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is functional singly, or along with cytotoxic drugs for of the therapy of metastatic CRC. 4,5 For instance, Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is functional singly, or along with cytotoxic drugs for of the therapy of metastatic CRC.…”

“…2,4 With the development of antitumour agents that are specifically targeted, chemotherapy against metastatic CRC has undergone significant improvement. 4,5 For instance, Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is functional singly, or along with cytotoxic drugs for of the therapy of metastatic CRC. [6][7][8] Thus, more personalized treatments are expected with the advent of specialized targeted therapy in the field of oncological procedures.…”